Powder of amino acids and method for producing the same

ABSTRACT

Dry powders of amino acids which exhibit great oral meltability and solubility, may be produced by spray drying a hydrous liquid of amino acids to produce a powder of amino acids, where the hydrous liquid of amino acids is prepared into the form of microfine liquid droplets in the presence of trehalose for spray drying, to obtain a powder having a mean particle size of 0.1 μm to 15 μm, as well as granulating and drying during the spray drying or after the spray drying, to obtain a granulated powder having a mean particle size of 20 μm to 1,000 μm.

CROSS REFERENCES TO RELATED APPLICATIONS

This application is a continuation of International Patent ApplicationNo. PCT/JPO3/01198, filed on Feb. 5, 2003, and claims priority toJapanese Patent Application No.046580/2002, filed on Feb. 22, 2002, andJapanese Patent Application No. 201848/2002, filed on Jul. 10, 2002, allof which are incorporated herein by reference in their entireties.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to powders of amino acids, which is amicrofine or granulated amino acid powder containing trehalose. Thepresent invention further relates to methods for producing such powders.

2. Discussion of the Background

Amino acids, amino acid salts, and amino acid derivatives (simplyreferred to as amino acids hereinafter) are widely used in medical dietsfor nutrition supplements, disease-specific amino acid preparations fororal administration and infusion for subject patients with renalimpairment and liver disorders, infantile nutritious compositions, dietfood materials, health foods, and functional foods. Further, amino acidsare used in cosmetics and in veterinary preparations for dosing toanimals, after being mixed in feeds and the like.

Trehalose, when contained in amino acids, not only serves as asaccharide nutrient but also suppresses the bittern taste of aminoacids, advantageously, without any occurrence of the Maillard reaction(browning reaction). Therefore, the presence of trehalose therein isrecommended. Specifically, those formulations described below are known.

For example, trehalose-coated (film) powders of amino acids are known,and may be prepared by one of the following methods. In a first method,a binder is added to a powder of amino acids in mixture to preparegranules by an extrusion granulation process, and the granules surfacesare then coated with trehalose as a coating material by fluidgranulation. In a second method, trehalose and a binder are added to apowder of amino acids in mixture for coating by fluid granulation, andspraying an aqueous ethanol solution over the resulting coated powderfor granulation (see, JP-A-6-227975).

Furthermore, an amino acid infusion containing trehalose and having thesame effects as described above is also known (see, JP-A-6-70718).

Also known are amino acid food products containing trehalose, which areadjusted to a pH 3.0 to 6.0 by the addition of sour agents such ascitric acid so as to prevent flavor deterioration due to heating of theamino acid, or flavor modification or color modification of the aminoacid during long-term storage. The test results of heating the hydrousamino acid-containing solution are disclosed (see, JP-A-2000-4836).

As compositions for use in the suppression of blood amino acid variationfollowing vigorous athletic motion, a hydrous solution of a compositionof amino acids and sugar is disclosed, which contains at least 13 typesof amino acids and trehalose. The hydrous solution is said to beeffective for the improvement of athletic potential and the ameliorationof fatigue (see, JP-A-2000-72669).

As described above, various findings exist about amino acid compositionscontaining trehalose, but only JP-A-6-227975 describes such a powder.Further, no amino acid powder with a high oral meltability, highsolubility, and masked taste is known. In particularly, there remains aneed for a dry power of a branched amino acid and a slightly solubleamino acid, which has improved oral meltability and solubility andsuppressed bitterness.

As production methods of dry powders, meanwhile, the spray dryingmethod, hot-air drying method, and freeze-drying method are known. Amongthem, the spray drying method is capable of producing microfineparticles, and is a dry method for recovering a dry powder of sphericaland spherical shell-shaped powder, by dispersing a solution or aparticle slurry into the form of microfine particles in hot air, wherethe spray method uses pressure nozzle, rotating disk, and two-fluidnozzle and the like. In many cases, the mean particle size of the drypowder is about 20 μm to 500 μm (see, Handbook of Chemistry andEngineering, revised sixth edition, p. 770, p. 780 (1999), issued byMaruzen), while in the pharmaceutical field, a production example ofmicrofine particles of 10 μm or less is introduced (see, JP-A-9-235238,JP-T-10-500672, and JP-A-11-114027). In recent years, a four-fluidnozzle has been developed, which has enabled mass-scale spray dryingwith a liquid droplet having a mean particle size of several micrometers(see, Chemical Apparatus, pp.60-65 (June, 2000), and U.S. Pat. No.2,797,080, and JP-A-2002-17337, etc.).

Similar to the powders containing microfine amino acids, an inhalationdry composition containing the pharmacologically active component,interferon, as the essential component and containing a hydrophobicamino acid selected from leucine, isoleucine, and valine at 60% or moreto less than 100% (mean particle size (volume-based distribution) of 0.1μm or more to 10 μm or less) is disclosed for the purpose of avoidingthe deliquescence of the inhalation dry composition, when left at a highhumidity (see, JP-A-9-235238). In Example 2 of JP-A-9-235238, a dryparticle powder is obtained as a control, by preparing a solutioncontaining 3.5 g of isoleucine, 0.7 g of serum albumin, 695.8 g ofdeionized water, and 300 g of ethanol for spray drying, and thenspraying the resulting solution with a spray dryer (aerodynamic meanparticle size of 0.9897 μm). However, this Example does not include anydescription of oral meltability, solubility, and taste masking.

Moreover, it is also desired that the production of powders of aminoacids by spray drying in such manner can be done on a mass scale; thatthe quality can be maintained; and that the oral meltability andsolubility of the resulting powders are great. Accordingly, thereremains a need for any improved process so as to satisfy theseproperties.

SUMMARY OF THE INVENTION

Accordingly, it is one object of the present invention to provide noveldry powders (meaning microfine powder or granulated powder) of aminoacids, which have great oral meltability and solubility and a highmasking effect of the taste.

It is another object of the present invention to provide novel methodsfor preparing such powders.

It is another object of the present invention to provide novel spraydrying methods for preparing such powders.

These and other objects, which will become apparent during the followingdetailed description, have been achieved by the inventors' discoverythat a dry powder of amino acids with great oral meltability andsolubility can be produced by a spray dryer capable of preparing anamino acid solution containing trehalose into the form of liquiddroplets of several micrometers (particle). Thus, the invention has beenachieved and provides the following embodiments:

(1) A method for producing a powder of amino acids, comprising spraydrying a hydrous liquid of amino acids to produce a powder of aminoacids, where the hydrous liquid of amino acids is prepared into the formof microfine liquid droplets in the presence of trehalose for spraydrying to prepare a powder having a mean particle size (Mean VolumeDiameter) of 0.1 μm to 15 μm.

(2) A method for producing a powder of amino acids, comprising spraydrying a hydrous liquid of amino acids to produce a powder of aminoacids, where the hydrous liquid of amino acids is prepared into the formof microfine liquid droplets in the presence of trehalose for spraydrying, and the resulting powder is then granulated and dried duringspray drying or after spray drying, to prepare a granulated powderhaving a mean particle size (Mean Volume Diameter) of 20 μm to 1,000 μm.

(3) A method for producing a powder of amino acids as described in (1)or (2), where the trehalose is added to the hydrous liquid of aminoacids or the trehalose is prepared in the form of a trehalose solutionat a microfine liquid droplet state to be fed into a spray dryer and/ora granulation dryer.

(4) A method for producing a powder of amino acids as described in (1)through (3), where the exhaust gas temperature during spray drying orgranulation drying is less than 97° C.

(5) A method for producing a powder of amino acids as described in (1)through (4), where the amino acids are slightly soluble amino acids.

(6) A method for producing a powder of amino acids as described in (5),where the amino acids are branched amino acids.

(7) A powder of amino acids, as obtained in a manner described in (1)through (6).

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete appreciation of the invention and many of the attendantadvantages thereof will be readily obtained as the same become betterunderstood by reference to the following detailed description whenconsidered in connection with the accompanying drawings, wherein:

FIG. 1 depicts two X-ray diffraction charts, in which the upper line isthe X-ray powder diffraction pattern of the spray dry granulated powderof Example 1 and the lower line is the X-ray powder diffraction patternof the mixed powder before drying of Comparative Example 2; and

FIG. 2 depicts three X-ray diffraction charts, in which the upper lineis the X-ray diffraction pattern of trehalose; the middle line is theX-ray diffraction pattern of “the mix powder of amino acids” used as theraw materials of Comparative Example 2; and the lower line is the X-raydiffraction pattern of hydroxypropyl cellulose.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Thus, in a first embodiment, the present invention provides novelpowders comprising amino acids and methods of producing such powders.The various aspects of the present invention are specifically describedbelow.

Amino Acids:

The amino acids to be used in accordance with the present inventioninclude amino acids, salts of amino acid, and amino acid derivatives,for example branched amino acids such as leucine, isoleucine, andvaline, sulfur-containing amino acids such as cystine and methionine,aromatic amino acids such as phenylalanine and tyrosine, heterocyclicamino acids such as tryptophan and histidine, acidic amino acids such asaspartic acid and glutamic acid, and various amino acid derivatives suchas sulfur-containing amino acid derivatives including taurine. Theseamino acids may be used singly or in combination of two or more thereof.

The subject hydrous solution of the amino acid(s) is in the solutionstate or a particle slurry solution state (for example, a slurrycontaining particles having a mean particle size (Mean Volume Diameter)of 0.1 μm to 15 μm), and the solvent may contain ethyl alcohol and thelike.

The amino acids to which the present invention is effectively appliedinclude amino acids relatively slightly soluble in water, such as aminoacids with a solubility of 9 g or less in 10 g of water at 20° C.Particularly, the amino acids preferable for the application of thepresent invention are slightly soluble amino acids. The presentinvention is preferably applied to amino acids with a solubility of 5 gor less in 100 g of water at 20° C. The present invention is applicableto leucine, isoleucine, cystine, phenylalanine, tyrosine, tryptophan,and aspartic acid, and salts thereof and derivatives thereof, inparticular.

The amount of the amino acid(s) to be used generally includes but is notspecifically limited to 20% by weight to 95% by weight in the drypowder. If necessary, the amount may be at 50% by weight to 95% byweight, 60% by weight to 95% by weight, or 70% by weight to 95% byweight. The amount to be used may satisfactorily be determined, takingaccount of the conditions of product design, namely the balance betweenthe amount of amino acid(s) required as effective ingredients and thespecific volume of the dry powder of amino acids.

Trehalose:

The raw material trehalose for use in accordance with the inventionincludes α,α-trehalose, α, β-trehalose, and β,β-trehalose. α,α-Trehaloseis preferable, because α,α-trehalose is a naturally occurring substanceand is now not costly. If necessary, the dihydrate thereof with almostno hygroscopicity over time may be used, satisfactorily. For example, acommercially available “Treha” (Hayashibara, Co., Ltd.) is listed andmay be used.

The amount of trehalose (on an anhydride basis) is 5% by weight to 80%by weight in the dry powder, satisfactorily. If necessary, the contentcan be 5% by weight to 50% by weight, 5% by weight to 40% by weight and5% by weight to 30% by weight. The amount of trehalose to be used may beadjusted to the conditions for product design, as described above.

The trehalose and the amino acid(s) may be mixed together to prepare amixture solution prior to spray drying. Otherwise, a hydrous solutioncontaining the amino acid(s) as the main components and a hydroussolution containing trehalose as the main component may besimultaneously sprayed together during spray drying. Alternatively,after a hydrous solution containing the amino acid(s) as the maincomponent(s) has been spray dried, a hydrous solution containingtrehalose as the main component may be sprayed and/or granulated as acoating agent and a binder, satisfactorily. If necessary, furtheradditives, other than trehalose, may be added satisfactorily as a matterof course.

Apparatus in Relation With Spray Drying:

As the spray drying apparatus for use in accordance with the presentinvention, commercially available apparatus can be used. For example, aspray drying apparatus which has a vertical parallel flow function ispreferable. In particular, when a system with a dehumidifying and dryingfunction is used, the productivity can be maintained, even under dryingconditions with dehumidification at low temperature, and the quality ofthe resulting dry powder can be maintained at a high level, preferably.As described below, for example, an apparatus capable of blowing a highvolume of dry dehumidified gas at 1% RH or less is particularlypreferable as the dehumidifying apparatus, which is for example a drydehumidifier BX series manufactured by Munsters K. K., and HCS seriesand HCP series manufactured by Nichias Corporation. Other suitable spraydrying apparatus include the micromist dryer MD series and the hybridgranulator series manufactured by Fujisaki Electric Co., Ltd., the FSDspray dryer with internal fluid layer as manufactured by NiroCorporation, the fluid granulation spray dryer and L-8 type spray dryermanufactured by O-gawara Chemical Engineering Machine Corporation, andthe DL-21 type and GB-21 type manufactured by Yamato Scientific Co.,Ltd.

In accordance with the present invention, it is important to carry outthe spray drying, using a spray nozzle capable of generating a liquiddroplet (microfine particle, single particle) having a mean particlesize (Mean Volume Diameter) of 0.1 μm or more to less than 20 μm.Specifically, it is important to carry out the drying using a spraydryer or a spray dry granulation apparatus with a spray nozzle capableof generating a large volume of liquid droplets having a mean particlesize (Mean Volume Diameter) of 0.1 μm or more to less than 20 μm,preferably 0.1 μm to 10 μm, and more preferably 1 μm to 8 μm. When theliquid droplet is dried, a dry powder having a mean particle size (MeanVolume Diameter) of 0.1 μm to 15 μm, preferably 0.1 μm to 7 μm, and morepreferably 0.7 μm to 6 μm is obtained. This is preferable with therespect to the control of the product quality and productivity, becausesuch liquid droplets can be dried under low-temperature conditionswithin a short time. For example, the four-fluid nozzle manufactured byFujisaki Electric Co., Ltd., which can spray a large volume (forexample, 1 kg/min) of liquid droplets of several micrometers (see, U.S.Pat. No. 2,797,080; Chemical Apparatus, 2000, No. 6, pp. ₆₀-₆₅) and thethree-fluid nozzle manufactured by Fukusen Production Corporation, whichcan spray a large volume (for example, 150 g/min) of liquid droplets of1 μm to 10 μm (see, Japanese Patent Publication Sho 63-5146) areincluded. The four-fluid nozzle is particularly preferable because alarge volume can be sprayed from the nozzle.

Granulation:

Furthermore, the spray dryer is preferably an apparatus with agranulation function or is additionally mounted with a granulation dryerif the spray dryer does not have such granulation function (referred toas “spray dry granulation apparatus”). Then, importantly, the resultingapparatus is of a specification to enable the granulated powder(aggregate particle powder) to be finally dried to the desired moisture.In the case of particles with such a small specific gravity such asthose of amino acids for use in accordance with the present invention,particles (Mean Volume Diameter) of 0.1 μm to 15 μm disadvantageouslyinvolve difficulty in handling. Therefore, preferably, a granulationdryer is additionally mounted in the inside of the spray dryer or in astate in communication with the spray dryer.

Appropriate conditions for the granulation size may satisfactorily beselected, depending on the need. For example, the granulation size is 20μm to 1,000 μm, and preferably 20 μm to 500 μm (Mean Volume Diameter).Satisfactorily, granulation is sometimes effected almost simultaneouslywith spray drying or in other cases, fluid granulation is effected afterspray drying or both fluid granulation and spray drying are effectedsimultaneously.

Then, preferably, the apparatus can carry out the final drying duringgranulation or immediately after granulation. As to the conditions priorto or after granulation, the conditions such as the outlet temperature(also referred to as “drying temperature” or “exhaust gas temperature”)of the spray dry granulation apparatus, the inlet temperature thereof,the outlet relative humidity thereof and the inlet relative humiditythereof are almost identical to those of spray drying conditionsdescribed below. In other words, the outlet temperature of the spray drygranulation apparatus is 20° C. to less than 97° C., preferably 20 to80° C., and more preferably 20 to 60° C. Additionally, the outletrelative humidity of the spray dry granulation apparatus is 1% RH to 50%RH, preferably 3% RH to 35% RH, and more preferably 6% RH to 30% RH.Further, the inlet temperature of the spray dry granulation apparatus is60 to 300° C., and preferably 70 to 180° C. Under conditions lower than60° C., the productivity is undesirably lowered. Under conditions above300° C., the quality of the resulting dry powder is undesirablydeteriorated. Furthermore, the inlet relative humidity of the spray drygranulation apparatus of the invention is 35% RH or less, preferably 15%RH or less, more preferably 7% RH or less, and most preferably 1% RH orless. These preferable conditions are selected with the respect to thecontrol of product quality such as the suppression of the Maillardreaction and with the respect to productivity improvement. Spray dryinggranulation apparatus with such granulation function include for examplethe “Hybrid Granulator Series as granulation apparatus on filter clothwith spray drying function equipped” manufactured by Fujisaki ElectricCo., Ltd.

Operation Conditions of the Spray Dryer:

Among the operation conditions of the spray dryer, the outlettemperature (also referred to as “drying temperature” or “exhaust gastemperature”) of the spray dryer is 20° C. to less than 97° C.,preferably 20 to 80° C., and more preferably 20 to 60° C. Attemperatures lower than 20° C., the productivity is undesirably lowered.Furthermore because the melting point of trehalose in the dihydrate formis 97° C., the outlet temperature is preferably set within a range notexceeding the melting point, with respect to quality control.

Meanwhile, the outlet relative humidity of the spray dryer set in thepresent invention is 1% RH to 50% RH, preferably 1% RH to 35% RH, andmore preferably 1% RH to 30% RH. The outlet relative humidity of thespray dryer as referred to in accordance with the present inventionmeans the relative humidity in the vicinity of the powder collectionpart of the spray dryer. For the spray dryer of the vertical parallelflow type, the outlet relative humidity (exhaust gas humidity) means therelative humidity at the exhaust part thereof. For the “HybridGranulator Series HGL-130 as granulation apparatus on filter cloth withspray drying function equipped” manufactured by Fujisaki Electric Co.,Ltd., for example, the outlet relative humidity means the relativehumidity (exhaust gas humidity) in the vicinity of the filter cloth atthe powder collection part of the apparatus.

Herein, the inlet temperature of the spray dryer is 60 to 300° C., andpreferably 70 to 180° C. Under conditions lower than 60° C., theproductivity is undesirably lowered. Under conditions above 300° C., thequality of the resulting dry powder is undesirably deteriorated.Furthermore, the inlet relative humidity of the spray dryer of thepresent invention is 35% RH or less, preferably 15% RH or less, morepreferably 7% RH or less, and most preferably 1% RH or less. Thesepreferable conditions for the inlet temperature, the outlet temperature,the inlet relative humidity, and the outlet relative humidity areselected with the respect to the control of product quality such as thesuppression of the Maillard reaction, and with respect to productivityimprovement.

The volume of dry gas, for example dry air for use in accordance withthe present invention is preferably 0.5 m/min or more, more preferably 1m/min to 5 m/min, and still more preferably 1 m/min to 3.5 m/min, withrespect to the improvement of the productivity of the dry powder.Herein, the volume of dry air means the air rate (m/min) in the spraydryer or at the cylinder part (the trunk part) of the body of the spraydry granulation apparatus. For the “Hybrid Granulator HGL-130 asgranulation apparatus on filter cloth with spray drying functionequipped” manufactured by Fujisaki Electric Co., Ltd., for example, thevolume means the filtration rate. Further, the liquid transfer rate ofthe raw material solutions such as the hydrous solution of amino acidsand the hydrous trehalose solution can be preset appropriately, inrelation with the inlet temperature, the outlet temperature, the exhaustgas humidity, the types of the raw material solutions, the desiredparticle size and the like. Additionally, the spraying pressure ispreferably 0.5 kg/cm² or more, more preferably 1 kg/cm² to 5 kg/cm², andstill more preferably 1 kg/cm² to 3 kg/cm².

Furthermore, the gas to be used in accordance with the invention ispreferably air, but may be a gas other than air, depending on the case.Inert gases, for example nitrogen gas and carbonate gas, can be used. Inthe case of addition of readily oxidizable substances or readilymodifiable substances, the use of an inert gas is effective and may bepreferred.

The moisture content (loss on drying) of the dry powder thus produced ispreferably 5 wt. % or less when dried at 60° C. for 5 hours. By spraydrying the hydrous solution containing trehalose and amino acids or thehydrous solution containing amino acids and the hydrous solutioncontaining trehalose in the form of liquid droplets having a meanparticle size of 0.1 μm or more to less than 20 μm, and preferably 0.1μm to 10 μm, the liquid droplet is instantly dried. By instant drying ata temperature lower than 97° C., and preferably at a temperature of 20to 60° C., the trehalose in the dry powder exists in a structure of analmost amorphous state. The existence in the amorphous state maypossibly generate excellent effects such as oral meltability of the drypowder, the solubility thereof, and the taste-masking effect thereof.Furthermore, some of amino acids are observed to have low crystallinity,according to the method of the present invention, which suggests anincrease of amorphous materials.

The dry powder thus produced can be used as it is or as an intermediatematerial, in the pharmaceutical field of, for example, oral or infusionamino acid preparations specific to individual diseases for subjectpatients with renal impairment or liver disorders, and the cosmeticfield, and the like. For example, the dry powder can be used in the formof powders, tablets, and capsules, as individual materials for foodssuch as sport drinks, diet food materials, health foods and functionalfoods, and amino acid-series cosmetics.

Other features of the invention will become apparent in the course ofthe following descriptions of exemplary embodiments which are given forillustration of the invention and are not intended to be limitingthereof.

EXAMPLES

Herein, the mean particle size of the microfine powders (single particlepowder generated from liquid droplet) were measured visually with amicroscope, while the mean particle size (Mean Volume Diameter) of thegranulated powders were measured with a dry particle size distributionmeasurement system of laser diffraction & scattering microtruck, 9320HRA manufactured by Honeywell Co., Ltd.).

Example 1

Water was added to 4.98% by weight of a mixture of branched amino acidshaving a mean particle size (Mean Volume Diameter) of 20 μm(leucine:isoleucine:valine=47% by weight:24% by weight:29% by weight;manufactured by Ajinomoto Co.); 4.98% by weight trehalose dihydrate(“Treha” manufactured by Hayashibara, Co., Ltd.); 0.45% by weight ofhydroxypropyl cellulose; and others, to prepare an aqueous solution ofamino acids at a solid concentration of 10.4% by weight.

The flow of dehumidified hot air having a relative humidity of 1% RH at25° C. (produced by the dry dehumidifier BX-600 type manufactured byMunsters, K. K.) was preset to 5.5 m³/min (filtration rate of about 3m/min), and spray drying and granulation were carried out with a“HGL-130 type as granulation apparatus on filter cloth with spray dryingfunction equipped” manufactured by Fujisaki Electric Co., Ltd. using theconditions of the inlet temperature of the spray dry granulationapparatus described below as set to 131 to 139° C. and the feed rate ofthe aqueous solution of amino acids as set to 6.7 to 7.3 kg/hr. With theexhaust gas temperature (outlet temperature) at 49 to 58° C. and theexhaust gas humidity (outlet relative humidity) at 20% RH to 30% RH, themean particle size of the microfine powder (single particle powdergenerated from the liquid droplets) was about 2 μm to 3 μm (diameter),as observed with a microscope. Then, the microfine powder was densifiedunder pressure into granules on the filter membrane for particlecollection, so that the dry powder granulated as the final product was apowder of amino acids, which had a mean particle size (Mean VolumeDiameter) of 40 μm (moisture content of 4 wt. %).

Comparative Example 1

An aqueous solution of amino acids (a solid concentration of 5.85% byweight) was prepared at ratios of 4.95% by weight of a powder ofbranched amino acids of a mean particle size (Mean Volume Diameter) of20 μm (leucine:isoleucine:valine=47% by weight:24% by weight:29% byweight; manufactured by Ajinomoto Co.); 0.45% by weight of sucrosepowder; 0.45% by weight of hydroxypropyl cellulose; and 94.15% by weightof water.

The flow of dehumidified hot air having a relative humidity of 1% RH at25° C. (produced by the dry dehumidifier BX-600 type manufactured byMunsters K.K.) was preset to 5.5 m³/min (filtration rate of about 3m/min), and spray drying and granulation were carried out with a“HGL-130 type as granulation apparatus on filter cloth with spray dryingfunction equipped” manufactured by Fujisaki Electric Co., Ltd., usingthe conditions of the inlet temperature of the spray dry granulationapparatus described below set to 130 to 137° C., and the supply rate ofaqueous amino acids solution set to 6.1 to 7.7 kg/hr. With the exhaustgas temperature (outlet temperature) at 49 to 61° C. and the exhaust gashumidity (outlet relative humidity) at 18% RH to 30% RH, the meanparticle size (diameter) of the microfine powder (single particle powdergenerated from the liquid droplets) was about 2 μm to 3 μm, as observedwith a microscope. Then, the microfine powder was densified underpressure into granules on the filter membrane for particle collection,so that the dry powder granulated as the final product was a powder ofamino acids, which had a mean particle size (Mean Volume Diameter) of 32μm (moisture content of 1 wt. %).

Comparative Example 2

Leucine, isoleucine, and valine. (manufactured by Ajinomoto Co.) wereindividually pulverized to a mean particle size (Mean Volume Diameter)of 20 μm, and were then mixed together uniformly at 47% by weight, 24%by weight and 29% by weight, respectively. Then, 47.8% by weight of thepowder of the amino acid mixture, 47.8% by weight of trehalose●dihydrate(“Treha” manufactured by Hayashibara, Co., Ltd.), and 4.4% by weight ofhydroxypropyl cellulose powder were uniformly mixed together.

Test Example 1

The granulated powder samples or powder mixture samples as recovered inExample 1, and Comparative Examples 1 and 2 were evaluated for theiroral meltability, solubility, the degree of bitterness, andsolidification property. The results are shown in Table 1. TABLE 1Evaluation results Comparative Comparative Items Example 1 Example 1Example 2 Oral meltability 5 2 3 Bitterness masking 5 2 3 Solubility 5.5min 6.00 min 14 min Solidification no problem no problem no problemNotes:The oral meltability and the degree of bitterness masking wereevaluated, while the scores of those of Comparative Example 2 wereranked as 3.1. Oral meltability (5: very good; 4: relatively good; 3: normal; 2:slightly poor; 1: poor)2. Degree of bitterness masking (5: very good; 4: relatively good; 3:normal; 2: slightly poor; 1: poor)3. Solubility: 250 ml off water at 16° C. was placed in a 300-ml beaker;an amount of a sample was measured to an amino acid content of 50 mg,and was then placed in the beaker under agitation at 300 rpm with amagnetic stirrer, F-616 Type (Tokyo Glass Kikai, Co., Ltd.), the timeuntil the sample was completely dissolved was determined and isreported.4. Solidification property: After individual samples were prepared, thesamples were pouched and sealed, and were then left to stand for 2weeks, to observe the solidified state.

As described above, the granulated powder containing trehalose(Example 1) had great oral meltability, great solubility, and a greateffect on bitterness masking. The granulated powder containing sugar(Comparative Example 1) had good solubility but poor oral meltabilitywithout any masking effect of bitterness. Additionally, the granulatedpowder tasted very powdery and had bad aftertaste.

Herein, the spray dry granulated powder containing trehalose (Example 1)is compared with the mixed powder of the powders and of the samecomposition (Comparative Example 2). The solubility of the mixed powderof the powders of Comparative Example 2 was similar to the solubility(13.5 minutes) of the “mix powder of amino acids”(leucine:isoleucine:valine=47% by weight:24% by weight:29% by weight) asthe raw material of Comparative Example 2 but was apparently poorer thanthe solubility of the spray dry granulated powder containing trehalose(Example 1). Furthermore, the oral meltability and thebitterness-masking effect of the mix powder of the powders ofComparative Example 2 were more or less worse than those of the spraydry granulated powder (Example 1).

Test Example 2

The spray dry granulated powder containing trehalose (Example 1), themixed powder of the powders (Comparative Example 2) and the individualraw material powders such as trehalose were analyzed by powder X raydiffraction. The results are shown in FIGS. 1 and 2. It was clearlyverified that trehalose in the spray dry granulated powder of Example 1was in an amorphous state, which apparently makes contributions to theoral meltability and the bitterness-masking effect. Additionally, thespray dry granulated powder (Example 1) lost the crystallinity essentialto amino acids. The spray dry granulated powder (Example 1) exhibitspartial crystallinity, but contains an amorphous fraction at a highcontent, when compared with Comparative Example 2.

In accordance with the present invention, a dry powder of amino acids ofhigh quality, such as improved oral meltability, solubility, and ataste-masking effect, can be obtained.

Obviously, numerous modifications and variations of the presentinvention are possible in light of the above teachings. It is thereforeto be understood that, within the scope of the appended claims, theinvention may be practiced otherwise than as specifically describedherein.

All patents and other references mentioned above are incorporated infull herein by this reference, the same as if set forth at length.

1. A method for producing a powder of one or more amino acids,comprising: (1) spray drying a hydrous liquid comprising at least oneamino acid to obtain a powder of said at least one amino acid, whereinsaid hydrous liquid comprising said at least one amino acids is preparedinto the form of microfine liquid droplets in the presence of trehalosefor spray drying to obtain a powder having a mean particle size of 0.1μm to 15 μm.
 2. The method of claim 1, wherein said trehalose is addedto said hydrous liquid comprising said at least one amino acid.
 3. Themethod of claim 1, wherein said trehalose is prepared into the form of atrehalose solution existing as microfine liquid droplets and is spraydried with said hydrous liquid comprising said at least one amino acid.4. The method of claim 1, wherein said spray drying is carried out undera condition of an exhaust gas temperature during spray drying of lessthan 97° C.
 5. The method of claim 1, wherein said at least one aminoacid is one or more slightly soluble amino acids.
 6. The method of claim1, wherein said at least one amino acid is one or more branched aminoacids.
 7. The method of claim 1, wherein said hydrous liquid comprisingat least one amino acid is a solution.
 8. The method of claim 1, whereinsaid hydrous liquid comprising at least one amino acid is a suspension.9. The method of claim 1, wherein said hydrous liquid comprising atleast one amino acid is an emulsion.
 10. A powder of one or more aminoacids, wherein said powder is prepared by a process according toclaim
 1. 11. A method for producing a powder of one or more amino acids,comprising: (1) spray drying a hydrous liquid comprising at least oneamino acid to obtain a powder of said at least one amino acid, whereinsaid hydrous liquid comprising at least one amino acid is prepared intothe form of microfine liquid droplets in the presence of trehalose forspray drying, and said powder of said at least one amino acid is thengranulated and dried, during spray drying or after spray drying, toobtain a granulated powder having a mean particle size of 20 μm to 1,000μm.
 12. The method of claim 11, wherein said trehalose is added to saidhydrous liquid comprising at least one amino acid.
 13. The method ofclaim 11, wherein said trehalose is prepared into the form of atrehalose solution existing as microfine liquid droplets and is spraydried and/or a granulated with said hydrous liquid comprising said atleast one amino acid.
 14. The method of claim 11, wherein said spraydrying or granulation is carried out under a condition of an exhaust gastemperature during spray drying of less than 97° C.
 15. The method ofclaim 11, wherein said at least one amino acid is a slightly solubleamino acid.
 16. The method of claim 11, wherein said at least one aminoacid is a branched amino acid.
 17. The method of claim 11, wherein saidhydrous liquid comprising at least one amino acid is a solution.
 18. Themethod of claim 11, wherein said hydrous liquid comprising at least oneamino acid is a suspension.
 19. The method of claim 11, wherein saidhydrous liquid comprising at least one amino acid is an emulsion.
 20. Apowder of one or more amino acids, wherein said powder is prepared by aprocess according to claim 11.